SF3B1 mutations in CLL and RS. Schematic diagram of the human SF3B1 gene (top) and protein (bottom) with its functional domains (PPP1R8 binding domain and HEAT repeats), and multiple alignment of the HEAT3, HEAT4, and HEAT5 amino acid sequences of the human SF3B1 protein with orthologous SF3B1 proteins (n = 15). Amino acids conserved among species are highlighted. Color-coded shapes indicate the position of the mutations found in CLL at diagnosis, in fludarabine-refractory CLL, and in RS.